PubMed Health⌕ Search

Biomedical subjects

J E Chelly

Publications and source records attributed to J E Chelly.

67 records · Page 4Linked to original sources
PubMed1987

Role of isoflurane on hemodynamic properties and disposition of nicardipine.

Nicardipine properties (30 micrograms/kg i.v.) were studied in a group of eight dogs awake and anesthetized with isoflurane 1.6% end-tidal. Awake, nicardipine produced a decrease in mean arterial pressure (-12 +/- 2 mm Hg) associated with an increase in cardiac output (1.63 +/- 0.2 liters/min), heart rate (75 +/- 9 beats/min), dP/dt (741 +/- 202 mm Hg/sec) and carotid (41 +/- 11 ml/min) and coronary blood flows (39 +/- 6 ml/min). During isoflurane, responses to nicardipine injections were less pronounced except for mean arterial pressure (-19 +/- 2 mm Hg) and reversed for dP/dt (-290 +/- 63 mm Hg/sec). In a second group of six conscious dogs, nicardipine (30 micrograms/kg i.v.) injected after ganglionic blockade (chlorisondamine, 2 mg/kg i.v.) elicited changes similar to those recorded during isoflurane anesthesia, data that demonstrated the importance of isoflurane-induced baroreflex blockade as a mechanism of the pharmacodynamic interactions between nicardipine and isoflurane. Isoflurane reduced nicardipine initial volume of distribution (11.6 +/- 1.2 vs. 8.9 +/- 0.8 liters), total clearance (28.5 +/- 2.9 vs. 19.2 +/- 2.1 liters/hr) and volume of distribution at steady state (50.0 +/- 11.3 vs. 29.2 +/- 3.7 liters, P less than .05). Nicardipine-induced hemodynamic changes were linearly correlated with the drug concentrations in plasma. In the presence of isoflurane, the slopes of these relationships were reduced for all hemodynamic variables except for mean arterial pressure, for which the slope was more pronounced, and dP/dt, for which the slope was reversed. In conclusion, isoflurane alters the drug plasma concentration-effect relationship of nicardipine as a result of both pharmacokinetic and pharmacodynamic interactions.

Animals↗
PubMed1987

Pharmacodynamic and pharmacokinetic interactions between lidocaine and verapamil.

Lidocaine (3 mg/kg i.v.) injected during steady-state verapamil infusions (3 micrograms/kg i.v.) induced slight and transient hemodynamic changes in nine conscious dogs. Systemic vascular resistance and left ventricular dP/dt decreased by 16% from 41 +/- 4 mm Hg/liter/min and by 20% from 2876 +/- 137 mm Hg/sec, respectively, whereas heart rate and cardiac output increased by 18% from 100 +/- 5 beats/min and by 17% from 2.5 +/- 0.2 liters/min, respectively. Simultaneously, lidocaine induced a transient but more pronounced decrease in verapamil plasma concentration of 48% from 60 +/- 3 ng/ml. This pharmacokinetic interaction was not the result of a lidocaine-induced decrease in the fraction of verapamil bound to plasma protein because in vitro lidocaine failed to displace verapamil from its protein binding site. Moreover, an increase in verapamil total clearance was not the only mechanism because steady-state lidocaine (6 mg/kg over 5 min followed by 60 micrograms/kg/min) in the presence of steady-state verapamil (200 micrograms/kg over 3 min followed by 3 micrograms/kg/min) also resulted in a transient decrease in verapamil plasma concentration from 59 +/- 9 to 23 +/- 2 ng/ml in six conscious dogs. Although verapamil did not affect lidocaine pharmacokinetics, in the presence of the steady-state lidocaine we recorded an increase in verapamil initial volume of distribution of 44% from 40 +/- 4 liters, and intercompartmental clearance increased by 88% from 101 +/- 20 liters/hr, combined with an increase in verapamil total clearance of 47% from 54 +/- 6 liters/hr (n = 6).

Animals↗
PubMed1986

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. I. Verapamil and halothane.

In order to assess the interaction between halothane and verapamil on the cardiovascular system, mongrel dogs were instrumented so that the following measurements could be made awake and under the influence of the drugs: aortic, left ventricular, and left atrial blood pressures; myocardial segment length shortening; heart rate and rhythm; and coronary, carotid, and renal blood flows. The effect of two infusion doses of verapamil (3 micrograms X kg-1 X min-1 and 6 micrograms X kg-1 X min-1 after 200 micrograms X kg-1 bolus) were examined awake. On a different day in the same dogs, two concentrations of halothane (1.2-low and 2.4-high % end-tidal) and the effect of the two infusion doses of verapamil during low and high halothane were studied. Thirty minutes of either infusion dose of verapamil produced only heart rate and electrocardiographic P-R interval increases in conscious dogs. Halothane produced dose-related decreases in mean aortic pressure, left ventricular maximum rate of tension development (dP/dt), and segment length shortening and increases in heart rate and left atrial pressure. Carotid blood flow was increased by low halothane concentrations and returned to control with high halothane concentrations. There were no significant changes in coronary or renal blood flow produced by halothane. Verapamil infusion during low halothane concentration produced minimal effects. However, both the 3 and 6 micrograms X kg-1 X min-1 verapamil doses further depressed hearts already depressed by the high concentrations of halothane and decreased renal and carotid blood flows.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Endotracheal↗
PubMed1986

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. II. Verapamil, enflurane, and isoflurane.

The effects of enflurane and isoflurane on the cardiovascular system and cellular calcium kinetics are somewhat different. Consequently, the interaction with the calcium channel blocking drug, verapamil, may also differ. In order to compare the anesthetics, the authors studied the effects of two infusion doses of verapamil (which produced plasma levels of 90 and 180 ng X ml-1) on cardiovascular dynamics and regional blood flow in awake dogs. On two other days, in the same dogs, the effects of approximately 1.1 and 2 MAC enflurane and isoflurane were first studied and then the same verapamil dose regimens while the same anesthetic concentrations were maintained. Verapamil produced only increases in heart rate and the P-R interval in the awake animal. The high dose of both anesthetics markedly decreased mean aortic pressure and left ventricular rate of tension development (dP/dt), and increased heart rate. However, only enflurane also decreased myocardial segment length shortening and increased left atrial pressure. Neither anesthetic alone affected coronary or renal blood flow, while both increased carotid blood flow at the low dose. Verapamil infusion during 1.2 MAC enflurane was more depressant than during 1.2 MAC isoflurane, but the combination of verapamil with 2 MAC concentration of both anesthetics was equally depressant. Both doses of both anesthetics increased plasma verapamil levels compared with the same verapamil dosing regimen awake. When these results are compared with those previously reported for halothane, the effects of verapamil during all three anesthetics are more similar than different.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Endotracheal↗
PubMed1986

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. III. Nicardipine and isoflurane.

To assess the interaction between isoflurane and the new calcium channel blocker, nicardipine, mongrel dogs were chronically instrumented to allow the following measurements: aortic, left ventricular and left atrial pressures; heart rate; cardiac output; and carotid, coronary, and renal blood flows. The hemodynamic effects of intravenous nicardipine 5, 10, 30, and 50 micrograms/kg were measured in awake dogs and during 1.6 and 3.0 per cent (end-tidal) isoflurane anesthesia. Nicardipine induced a dose-dependent fall in mean arterial pressure in both awake dogs and during 1.6 and 3.0 per cent isoflurane anesthesia. Heart rate and cardiac output were increased in proportion to the nicardipine dose in the awake dogs and, to a lesser degree, in the dogs anesthetized with 1.6 per cent isoflurane, but did not change during 3.0 per cent isoflurane anesthesia. Left atrial pressure was unchanged by nicardipine in awake dogs and during anesthesia. Left ventricular maximum rate of tension development (dP/dt) increased in awake dogs and decreased during anesthesia. Coronary blood flow increased dose dependently without anesthesia, and, to a smaller degree, during anesthesia. Nicardipine increased carotid blood flow without anesthesia, whereas it was unchanged during anesthesia. Renal blood flow was unchanged in awake dogs and decreased during anesthesia. The authors conclude that nicardipine is a potent vasodilator that minimally affects cardiac function and regional blood flow in the presence of isoflurane. The interactions between nicardipine and isoflurane are mainly the result of the isoflurane-induced inhibition of the reflex tachycardia elicited by nicardipine.

Animals↗
PubMed1986

Effects of hydralazine on regional blood flow in conscious dogs.

This study was designed to assess the effects of hydralazine administered p.o. on regional circulation, including the carotid, coronary and renal arteries. Hydralazine in doses of 0.5, 1 and 5 mg/kg (p.o., n = 5) increased coronary blood flow by 9 +/- 4, 15 +/- 4 and 18 +/- 3 ml/min (P less than .05), respectively, and renal blood flow by 17 +/- 7, 26 +/- 12, 36 +/- 10 ml/min (P less than .05), respectively, but had no effects on carotid blood flow in conscious, normotensive dogs. The increase in coronary blood flow was correlated linearly with the rate pressure product (r = 0.581, P less than .05). After ganglionic blockade using chlorisondamine (2 mg/kg i.v.), hydralazine in a dose of 1 mg/kg (p.o., n = 4) increased renal blood flow by 45 +/- 6 ml/min (P less than .05), whereas mean arterial pressure, cardiac output, heart rate and coronary blood flow remained essentially unchanged. The increase in renal blood flow produced by hydralazine (1 mg/kg p.o., n = 6) was prevented by pretreatment with a cyclooxygenase inhibitor, indomethacin (2 mg/kg, i.v.). In vitro, hydralazine failed to relax segments of carotid, coronary and renal arteries. Our data indicate that hydralazine is a direct and preferential renal vasodilator. It produces an indirect coronary vasodilation related to an increase in myocardial oxygen demand. Its effect on renal circulation appears to be dependent on the prostaglandin system and is related mainly to a relaxation of arteriolar resistant vessels.

Animals↗
PubMed1986

Effects of inhalational anesthetics on verapamil pharmacokinetics in dogs.

Six dogs were chronically instrumented in order to collect aortic blood samples and record mean arterial pressure, cardiac output and heart rate. Each animal received verapamil 200 micrograms X kg-1 by 10-min intravenous infusions on four occasions in random sequence: awake, and during halothane 1.2%, enflurane 2.5%, and isoflurane 1.6% anesthesia. Rate of initial distribution of verapamil was reduced during anesthetic exposure. Verapamil intercompartmental clearance from the central compartment to the peripheral compartment was decreased during exposure to halothane and isoflurane, and tended to decrease during enflurane exposure as well. Verapamil terminal volume of distribution at steady-state was reduced by halothane, enflurane, and isoflurane exposure as compared with awake: 65 +/- 10, 80 +/- 9, and 93 +/- 191, respectively, versus 132 +/- 121 (mean +/- SEM; P less than 0.05). Verapamil total clearance was also reduced by halothane, enflurane, and isoflurane as compared with awake: 37 +/- 4, 39 +/- 2 and 41 +/- 31 X h-1, respectively, versus 64 +/- 71 X h-1 (P less than 0.05). Verapamil administered to awake animals resulted in a decrease from baseline in mean arterial pressure; 95 +/- 8 mmHg versus 108 +/- 4 mmHg (P less than 0.05): and an increase in cardiac output; 2.60 +/- 0.33 1 X min-1 versus 1.93 +/- 0.22 1 X min-1 (P less than 0.05). During halothane, enflurane, and isoflurane anesthesia, verapamil administration resulted in a similar decrease in mean arterial pressure; however cardiac output decreased, in contrast to the increase noted in awake animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1985

Hemodynamic effects of the intraventricular administration of angiotensin II and renin in awake dogs.

This study was undertaken to investigate the hemodynamic changes induced by intraventricular injections of angiotensin II (A-II), 1 to 100 ng/kg/min, and renin in doses of 0.025 to 0.3 units (u) in conscious instrumented dogs. Angiotensin II produced a dose-related increase in mean arterial pressure; however, only the highest dose produced a significant increase of 23 +/- 6 mmHg. In contrast, renin did not significantly alter mean arterial pressure in the doses administered but 0.1 and 0.3 u induced a significant increase in systolic arterial blood pressure of 10 +/- 2 and 17 +/- 4 mmHg, respectively. Neither A-II nor renin affected heart rate, dP/dt or carotid, coronary or renal blood flows. These data suggest that in conscious dogs, the threshold level of A-II necessary to induce substantial hemodynamic changes is greater than the amount of A-II that can be acutely generated by activation of angiotensinogen. In addition, the present data suggest that the magnitude of the response is dependent on the availability of the substrate rather than the dose of renin injected centrally into conscious dogs.

Angiotensin II↗
PubMed1984

Effects of brain renin-angiotensin on cardiovascular function and saline intake in awake dogs.

Initial studies were undertaken to investigate the effects of prolonged administration of angiotensin II (AII), 1 micrograms twice daily, via the lateral ventricles to mongrel dogs on arterial blood pressure and to determine if sodium intake was essential for the development of hypertension. Increasing AII levels in the cerebrospinal fluid for a prolonged period of time produced a sustained hypertensive state only in those dogs in which the daily intake of sodium was increased. The hypertension appeared to be due to an increase in total peripheral resistance. Central administration of AII increased both fluid intake and urine output. In order to assess the hemodynamic effects of increasing endogenous brain AII, renin was injected in doses of 0.025, 0.05, 0.1 and 0.3 units (from porcine kidney) into the lateral ventricles of chronically instrumented awake dogs. Hemodynamic variables were recorded prior to and one and 2 h after the central administration of renin. Renin produced a dose-dependent increase in mean arterial pressure with no significant change in heart rate or carotid, coronary and renal blood flow velocities. Chronic intraventricular administration of renin, 0.15 units twice daily to awake instrumented dogs receiving saline as the drinking fluid, markedly increased the daily intake of saline and increased diastolic and systolic blood pressure without increasing heart rate or carotid, coronary or renal blood flow velocities. There appears to be a direct significant relationship between the increase in mean blood pressure due to the intraventricular administration of renin and the volume of saline consumed.

Angiotensin II↗
PubMed1984

Use of nitroprusside during surgery for thoracoabdominal aortic aneurysm.

To assess the effects of sodium nitroprusside on the deleterious hemodynamic effects of clamping and unclamping of the aorta during resection of thoracoabdominal aortic aneurysm without the use of a shunt, 50 patients were studied. The risk factors included coronary artery disease (44%) associated with previous myocardial infarction (28%), hypertension (70%), congestive heart failure (6%), chronic obstructive pulmonary disease (34%), asthma (2%), and renal insufficiency (2%). Sodium nitroprusside infusion (3 micrograms/kg/min) was started before clamping and discontinued before unclamping of the aorta. The infusion rate was adjusted to maintain blood pressure and pulmonary capillary wedge pressure within the range of control. During cross-clamping cardiac index in the patients remained unchanged and even increased on unclamping, suggesting that left ventricular function was efficiently protected during these periods. All the patients survived the surgery, and the 30 day mortality was only 4%. Our data indicate that major aortic surgery can be carried out safely with the use of nitroprusside rather than of mechanical techniques to provide proximal decompression.

Adult↗
PubMedDate not supplied

Blocks at the wrist provide effective anesthesia for carpal tunnel release.

PURPOSE: Distal blocks are not recommended even for a short procedure when a tourniquet is used. This study was designed to evaluate the tolerance, effectiveness, patient acceptance and safety of distal blocks at the wrist. METHODS: Consecutive patients (n=273, mean age 53 +/-15 yr) undergoing endoscopic carpal tunnel release with a pneumatic tourniquet were included in this study. The median nerve was blocked 6 cm above the wrist crease by injecting 10 mL of 2% lidocaine and 0.5% bupivacaine (v/v). The ulnar nerve was blocked by injecting 8 mL of the same anesthetic mixture below the flexor carpi ulnaris tendon 6 cm above the wrist crease. Finally, 2 mL of local anesthetic were infiltrated sc and laterally below the crease to block the musculocutaneous nerve. The intensity of the block was evaluated after five, ten and 20 min. In addition, pain associated with block performance and tolerance of the tourniquet were evaluated. Finally, neurological complications associated with this technique were investigated. Data are presented as means +/- SD. RESULTS: At ten minutes after the block was performed, 9% and 32% of patients required an additional injection to complete the block in the median and ulnar territories, respectively. In more than 75% of patients, performance of the block was associated with either no or mild pain. The tourniquet was inflated for 12.6 +/- 5.4 min and was well tolerated in 99% of patients. Finally, neither transient nor permanent neurological deficit were recorded postoperatively. CONCLUSION: Blocks at the wrist are effective, well accepted by the patient and safe when a pneumatic tourniquet is used for a short procedure.

Aged↗